RESUMEN
Inflammatory bowel diseases (IBDs) are chronic intestinal disorders often characterized by a dysregulation of T cells, specifically T helper (Th) 1, 17 and T regulatory (Treg) repertoire. Increasing evidence demonstrates that dietary polyphenols from Mangifera indica L. extract (MIE, commonly known as mango) mitigate intestinal inflammation and splenic Th17/Treg ratio. In this study, we aimed to dissect the immunomodulatory and anti-inflammatory properties of MIE using a reverse translational approach, by initially using blood from an adult IBD inception cohort and then investigating the mechanism of action in a preclinical model of T cell-driven colitis. Of clinical relevance, MIE modulates TNF-α and IL-17 levels in LPS spiked sera from IBD patients as an ex vivo model of intestinal barrier breakdown. Preclinically, therapeutic administration of MIE significantly reduced colitis severity, pathogenic T-cell intestinal infiltrate and intestinal pro-inflammatory mediators (IL-6, IL-17A, TNF-α, IL-2, IL-22). Moreover, MIE reversed colitis-induced gut permeability and restored tight junction functionality and intestinal metabolites. Mechanistic insights revealed MIE had direct effects on blood vascular endothelial cells, blocking TNF-α/IFN-γ-induced up-regulation of COX-2 and the DP2 receptors. Collectively, we demonstrate the therapeutic potential of MIE to reverse the immunological perturbance during the onset of colitis and dampen the systemic inflammatory response, paving the way for its clinical use as nutraceutical and/or functional food.
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Colitis , Enfermedades Inflamatorias del Intestino , Mangifera , Adulto , Humanos , Animales , Factor de Necrosis Tumoral alfa/metabolismo , Células Endoteliales/metabolismo , Mucosa Intestinal , Modelos Animales de EnfermedadRESUMEN
Microsystems represent an alternative but proficient approach of analysis outside the laboratory, and their use could help in reducing the impact of pre-analytical errors, in particular in challenging newborn samples. The study purpose is to compare the Horiba Microsemi CRP LC-767G system for rapid 3-part complete blood count (CBC) and C-reactive protein (CRP) determination with the laboratory reference systems (respectively Sysmex XN-9100™ and Roche Cobas® c702) in samples of adult patients and newborns hospitalized in the neonatal intensive care unit (NICU) samples. The comparison between the analyzers was performed through Passing-Bablok regression analysis and Bland-Altman plot. One hundred eighty-three blood samples were analyzed. The regression analysis results, performed in the newborn (n = 70) and in adult (n = 113) populations, showed a good agreement between the instruments. The evaluation of the Bland-Altman plots showed comparable values of bias < 10% for most of the parameters, but not for MPV, lymphocyte, and monocyte count. CONCLUSION: The comparison between the Microsemi CRP LC-767G system and the laboratory instrumentations demonstrated comparable results. The Microsemi CRP LC-767G system provides reliable analytical data and faster turnaround time, particularly useful in NICU. WHAT IS KNOWN: ⢠Microsystems for point-of-care testing (POCT) represent an alternative but proficient approach of analysis outside the laboratory, in order to perform a rapid, safe, and exhaustive evaluation for critical patients' management, acting as a valid support for treatment in acute care. WHAT IS NEW: ⢠The Microsemi CRP LC-767G system can represent an alternative but effective testing approach outside the laboratory, particularly in NICU, to reduce the impact of pre-analytical errors on newborn samples.
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Proteína C-Reactiva , Unidades de Cuidado Intensivo Neonatal , Humanos , Recién Nacido , Proteína C-Reactiva/análisis , Recuento de Células Sanguíneas/instrumentación , Recuento de Células Sanguíneas/métodos , Recuento de Células Sanguíneas/estadística & datos numéricos , Adulto , Masculino , Femenino , Hospitales Universitarios , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
We have previously demonstrated that the vasopressin type 2 receptor (AVPR2) antagonist tolvaptan reduces cell proliferation and invasion and triggers apoptosis in different human cancer cell lines. To study this effect in vivo, a xenograft model of small cell lung cancer was developed in Fox1nu/nu nude mice through the subcutaneous inoculation of H69 cells, which express AVPR2. One group of mice (n = 5) was treated with tolvaptan for 60 days, whereas one group (n = 5) served as the control. A reduced growth was observed in the tolvaptan group in which the mean tumor volume was significantly smaller on day 60 compared to the control group. In the latter group, a significantly lower survival was observed. The analysis of excised tumors revealed that tolvaptan effectively inhibited the cAMP/PKA and PI3K/AKT signaling pathways. The expression of the proliferative marker proliferating cell nuclear antigen (PCNA) was significantly lower in tumors excised from tolvaptan-treated mice, whereas the expression levels of the apoptotic marker caspase-3 were higher than those in control animals. Furthermore, tumor vascularization was significantly lower in the tolvaptan group. Overall, these findings suggest that tolvaptan counteracts tumor progression in vivo and, if confirmed, might indicate a possible role of this molecule as an adjuvant in anticancer strategies.
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Antagonistas de los Receptores de Hormonas Antidiuréticas , Proliferación Celular , Neoplasias Pulmonares , Ratones Desnudos , Receptores de Vasopresinas , Carcinoma Pulmonar de Células Pequeñas , Tolvaptán , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Tolvaptán/farmacología , Tolvaptán/uso terapéutico , Antagonistas de los Receptores de Hormonas Antidiuréticas/farmacología , Ratones , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Humanos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Carcinoma Pulmonar de Células Pequeñas/patología , Receptores de Vasopresinas/metabolismo , Apoptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
Common variable immunodeficiency (CVID) is the most frequent primary antibody deficiency whereby follicular helper T (Tfh) cells fail to establish productive responses with B cells in germinal centers. Here, we analyzed the frequency, phenotype, transcriptome, and function of circulating Tfh (cTfh) cells in CVID patients displaying autoimmunity as an additional phenotype. A group of patients showed a high frequency of cTfh1 cells and a prominent expression of PD-1 and ICOS as well as a cTfh mRNA signature consistent with highly activated, but exhausted, senescent, and apoptotic cells. Plasmatic CXCL13 levels were elevated in this group and positively correlated with cTfh1 cell frequency and PD-1 levels. Monoallelic variants in RTEL1, a telomere length- and DNA repair-related gene, were identified in four patients belonging to this group. Their blood lymphocytes showed shortened telomeres, while their cTfh were more prone to apoptosis. These data point toward a novel pathogenetic mechanism in CVID, whereby alterations in DNA repair and telomere elongation might predispose to antibody deficiency. A Th1, highly activated but exhausted and apoptotic cTfh phenotype was associated with this form of CVID.
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Inmunodeficiencia Variable Común , Apoptosis/genética , Inmunodeficiencia Variable Común/genética , Humanos , Receptor de Muerte Celular Programada 1/genética , Células T Auxiliares Foliculares , Linfocitos T Colaboradores-InductoresRESUMEN
Gadolinium-based contrast agents (GBCAs) are massively employed in radiology to increase the diagnostic power of MRI. However, investigations aiming at detecting possible metabolic perturbations or adverse health effects due to gadolinium deposition are still lacking. In this work, aqueous organs extract and plasma samples were analyzed by GC-MS and 1H-NMR, respectively, to investigate the effects of multiple administrations of one linear (Omniscan) and one macrocyclic (ProHance) GBCA, on the main metabolic pathways in healthy mice. Multivariate analysis revealed that plasma metabolome was not differently perturbed by the two GBCAs, while, the multiorgan analysis displayed a clear separation of the Omniscan-treated from the control and the ProHance-treated groups. Interestingly, the most affected organs were the brain, cerebellum and liver. Thus, this work paves the way to both the safest use of the commercially available GBCAs and the development of new GBCAs characterized by lower general toxicity.
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Gadolinio , Compuestos Organometálicos , Ratones , Animales , Gadolinio/toxicidad , Gadolinio/metabolismo , Gadolinio DTPA/metabolismo , Compuestos Organometálicos/toxicidad , Medios de Contraste/toxicidad , Medios de Contraste/metabolismo , Encéfalo/metabolismo , Imagen por Resonancia MagnéticaRESUMEN
Background and Objectives: Underpowered immune response to vaccines against SARS-CoV-2 was observed in solid organ transplant (SOT) recipients. A novel combination of monoclonal antibodies tixagevimab-cilgavimab (TGM/CGM) received authorization as pre-exposure prophylaxis (PrEP) in those with reduced response to vaccine. We aimed to evaluate the response rate to COVID-19 vaccination in kidney transplant (KT), compared to liver transplant (LT) recipients, and the efficacy and safety of PrEP with TGM/CGM. Material and Methods: Between March and November 2022, adult KT and LT recipients who had completed the vaccination schedule (3 doses) were tested for anti-SARS-CoV-2 antibodies titer. SOT recipients with anti-SARS-CoV-2 titer ≥ 100 IU/mL were considered protected against infection, while those with titer < 100 UI/mL were defined non-protected. Patients with inadequate response were invited to PrEP. Results: In total, 306 patients were enrolled [KT:197 (64.4%), LT:109 (35.6%)]. After the complete scheme of vaccination, 246 (80.3%) patients developed a protective titer, while 60 (19.6%) did not have a protective titer. KT recipients had a lower rate of protective anti-COVID-19 titer compared to LT patients [149 (75.6%) vs. 97 (89.0%), p = 0.004]. Recipients with non-protective anti-COVID-19 titer received mainly tacrolimus-based regimen associated with mycophenolate mofetil (MMF) (70%) e steroids (46.7%) as maintenance immunosuppression, while those treated with everolimus were associated with higher protective titer. Of 35 (58.3%) patients who received PrEP, within 12 months, 6 (17.1%) (all KT) developed pauci-symptomatic COVID-19 disease, while 15/25 (60%) of non-responders, who did not receive the prophylaxis, developed COVID-19 disease. After PrEP, hospitalization rate was lower (2.8% vs. 16%), and no adverse events, neither graft loss nor rejection, were observed. Conclusions: Despite complete COVID-19 vaccination, SOT recipients might be not protected from the SARS-CoV-2 infection, especially after KT. In non-protected SOT patients, the subsequent pre-exposure prophylaxis with combination of monoclonal antibodies (TGM/CGM) might be an efficacy and safe strategy to prevent COVID-19 severe disease and hospitalization.
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COVID-19 , Trasplante de Hígado , Profilaxis Pre-Exposición , Adulto , Humanos , Vacunas contra la COVID-19/uso terapéutico , Riñón , Anticuerpos Monoclonales , Vacunación , Anticuerpos Antivirales , COVID-19/prevención & control , SARS-CoV-2RESUMEN
OBJECTIVES: To assess the efficacy of the novel anti-IL-23 monoclonal antibody guselkumab in a real-life observational cohort of patients with early PsA. METHODS: We conducted an observational study on patients with early PsA followed by the joint dermatology-rheumatology clinics of two Italian centres starting therapy with guselkumab for severe skin involvement. Each patient was evaluated at baseline and every 24 weeks for one year, recording Disease Activity Index for PsA (DAPSA), PASI, VAS Pain, VAS Prutitus, Patient's Global Assessment (PtGA) and assessing DAPSA response. RESULTS: Twenty-four patients were recruited (16 women). The mean duration of skin disease was 12.5 years (CI 8; 17), but all patients had a shorter articular disease duration, 21.29 months (CI 15.9; 26.68). At baseline, all patients displayed a moderate cutaneous disease with a mean PASI of 15.2 (CI 11.7-18.6) and high disease activity, characterized by mean DAPSA of 26.84 (CI 22.49-31.19). An inflammatory low back pain was reported by five patients (20%) with a mean BASDAI 5.1 (CI 4,38-5,85) at baseline. The majority of guselkumab-treated patients (n = 18; 75%) reached DAPSA remission or DAPSA low disease activity after six months. Seventeen out of 24 patients completed 12 months of treatment, 11 of them (65%) in low disease activity, six (35%) in remission. All patients with axial disease reported improvement of inflammatory low back pain at week 24 with a mean BASDAI 2.98 (CI 2,18- 3,77). No significant side effects were reported. CONCLUSIONS: Real-life data on a cohort of early PsA patients confirm the efficacy and safety of guselkumab on peripheral and axial manifestations.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Artificial Intelligence applied to Structural Health Monitoring (SHM) has provided considerable advantages in the accuracy and quality of the estimated structural integrity. Nevertheless, several challenges still need to be tackled in the SHM field, which extended the monitoring process beyond the mere data analytics and structural assessment task. Besides, one of the open problems in the field relates to the communication layer of the sensor networks since the continuous collection of long time series from multiple sensing units rapidly consumes the available memory resources, and requires complicated protocol to avoid network congestion. In this scenario, the present work presents a comprehensive framework for vibration-based diagnostics, in which data compression techniques are firstly introduced as a means to shrink the dimension of the data to be managed through the system. Then, neural network models solving binary classification problems were implemented for the sake of damage detection, also encompassing the influence of environmental factors in the evaluation of the structural status. Moreover, the potential degradation induced by the usage of low cost sensors on the adopted framework was evaluated: Additional analyses were performed in which experimental data were corrupted with the noise characterizing MEMS sensors. The proposed solutions were tested with experimental data from the Z24 bridge use case, proving that the amalgam of data compression, optimized (i.e., low complexity) machine learning architectures and environmental information allows to attain high classification scores, i.e., accuracy and precision greater than 96% and 95%, respectively.
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Compresión de Datos , Vibración , Inteligencia Artificial , Aprendizaje Automático , Redes Neurales de la ComputaciónRESUMEN
The outbreak of COVID-19 led to a reduction in the number of organ transplant interventions in most Countries. In April 2020, at the Tor Vergata University in Rome, Italy, two patients on the waiting list for kidney transplantation (KT) declined a deceased donor's kidney offer. Therefore, between April 20 and 25, 2020, we conducted a telephone survey among our 247 KT waitlist patients. Our aim was to explore: (a) the COVID-19 diffusion among them and (b) their current willingness to be transplanted in case of a kidney offer from a deceased donor. Two hundred and forty-three patients participated in a phone interview. One patient had died from COVID-19. Eighty-five (35%) KT candidates would decline any kidney offer, in most cases until the end of the COVID-19 pandemic. Upon a multivariate analysis, female gender (OR = 2.25, 95% CI = 1.26-4.03, P = .006), high cardiovascular risk (OR = 2.33, 95% CI = 1.06-5.08, P = .034), a waiting list time <3 years (OR = 0.375, 95% CI = 0.15-0.95, P = .04), and the need to be transferred to another hospital for HD (OR = 2.56, 95% CI = 1.10-5.9, P = .03) were associated with such refusal. The COVID-19 pandemic led to a fear of transplantation in a third of the KT candidates. Proactive educational webinars could be a useful tool to remove, or at least lessen, any doubts on the part of KT candidates and to avoid losing the opportunity to quit dialysis.
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Actitud Frente a la Salud , COVID-19 , Fallo Renal Crónico/terapia , Trasplante de Riñón , Negativa del Paciente al Tratamiento , Listas de Espera , Anciano , Toma de Decisiones , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Italia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Diálisis Peritoneal , Diálisis Renal , SARS-CoV-2 , Factores Sexuales , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
Oral ferrous salts are standard treatment for children with iron deficiency anemia (IDA). The objective of our study was to monitor oral iron therapy in children, aged 3 months-12 years, with IDA. We prospectively collected clinical and hematological data of children with IDA, from 15 AIEOP (Associazione Italiana di Ematologia ed. Oncologia Pediatrica) centers. Response was measured by the increase of Hb from baseline. Of the 107 analyzed patients, 18 received ferrous gluconate/sulfate 2 mg/kg (ferrous 2), 7 ferrous gluconate/sulfate 4 mg/kg (ferrous 4), 7 ferric iron salts 2 mg/kg (ferric), 62 bis-glycinate iron 0.45 mg/kg (glycinate), and 13 liposomal iron 0.7-1.4 mg/kg (liposomal). Increase in reticulocytes was evident at 3 days, while Hb increase appeared at 2 weeks. Gain of Hb at 2 and 8 weeks revealed a higher median increase in both ferrous 2 and ferrous 4 groups. Gastro-intestinal side effects were reported in 16% (ferrous 2), 14% (ferrous 4), 6% (glycinate), and 0 (ferric and liposomal) patients. The reticulocyte counts significantly increased after 3 days from the start of oral iron supplementation. Bis-glycinate iron formulation had a good efficacy/safety profile and offers an acceptable alternative to ferrous iron preparations.
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Anemia Ferropénica/tratamiento farmacológico , Compuestos Ferrosos/administración & dosificación , Administración Oral , Adolescente , Anemia Ferropénica/sangre , Niño , Preescolar , Femenino , Compuestos Ferrosos/efectos adversos , Humanos , Lactante , Hierro/administración & dosificación , Hierro/efectos adversos , Masculino , Estudios ProspectivosRESUMEN
BACKGROUND: Purine nucleoside phosphorylase (PNP) deficiency has been recently introduced in the newborn screening program in Tuscany. In order to improve the PNP screening efficiency, we developed a 2nd tier test to quantify PNP primary markers deoxyguanosine (dGuo) and deoxyinosine (dIno). METHODS: Dried blood spots (DBS) samples were extracted with 200 µL of methanol and 100 µL of water (by two steps). Internal standards were added at a final concentration of 10 µmol/L. After extraction, samples were analysed by LC-MS/MS. The chromatographic run was performed in gradient mode by using a Synergi Fusion column. RESULTS: The assay was linear over a concentration range of 0.05-50 µmol/L (R2>0.999) for dGuo and 0.5-50 µmol/L (R2>0.998) for dIno. Intra- and interassay imprecision (mean CVs) for dIno and dGuo ranged from 2.9% to 12%. Limit of quantitaion (LOQ) were found to be 0.05 µmol/L and 0.5 µmol/L for dGuo and dIno, respectively. The reference ranges, obtained by measuring dGuo and dIno concentrations on DBS, were close to zero for both biomarkers. Moreover, DBS samples from seven patients with confirmed PNP were retrospectively evaluated and correctly identified. CONCLUSIONS: The LC-MS/MS method can reliably measure dIno and dGuo in DBS for the diagnosis of PNP. Validation data confirm the present method is characterised by good reproducibility, accuracy and imprecision for the quantitation of dIno and dGuo. The assay also appears suitable for use in monitoring treatment of PNP patients.
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Pruebas con Sangre Seca , Tamizaje Neonatal , Purina-Nucleósido Fosforilasa/deficiencia , Errores Innatos del Metabolismo de la Purina-Pirimidina/sangre , Adulto , Cromatografía Liquida , Humanos , Recién Nacido , Enfermedades de Inmunodeficiencia Primaria , Purina-Nucleósido Fosforilasa/sangre , Purina-Nucleósido Fosforilasa/metabolismo , Errores Innatos del Metabolismo de la Purina-Pirimidina/diagnóstico , Errores Innatos del Metabolismo de la Purina-Pirimidina/metabolismo , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: Purine nucleoside phosphorylase (PNP) deficiency is a rare form of autosomal recessive combined primary immunodeficiency caused by a enzyme defect leading to the accumulation of inosine, 2'-deoxy-inosine (dIno), guanosine, and 2'-deoxy-guanosine (dGuo) in all cells, especially lymphocytes. Treatments are available and curative for PNP deficiency, but their efficacy depends on the early approach. PNP-combined immunodeficiency complies with the criteria for inclusion in a newborn screening program. OBJECTIVE: This study evaluate whether mass spectrometry can identify metabolite abnormalities in dried blood spots (DBSs) from affected patients, with the final goal of individuating the disease at birth during routine newborn screening. METHODS: DBS samples from 9 patients with genetically confirmed PNP-combined immunodeficiency, 10,000 DBS samples from healthy newborns, and 240 DBSs from healthy donors of different age ranges were examined. Inosine, dIno, guanosine, and dGuo were tested by using tandem mass spectrometry (TMS). T-cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) levels were evaluated by using quantitative RT-PCR only for the 2 patients (patients 8 and 9) whose neonatal DBSs were available. RESULTS: Mean levels of guanosine, inosine, dGuo, and dIno were 4.4, 133.3, 3.6, and 3.8 µmol/L, respectively, in affected patients. No indeterminate or false-positive results were found. In patient 8 TREC levels were borderline and KREC levels were abnormal; in patient 9 TRECs were undetectable, whereas KREC levels were normal. CONCLUSION: TMS is a valid method for diagnosis of PNP deficiency on DBSs of affected patients at a negligible cost. TMS identifies newborns with PNP deficiency, whereas TREC or KREC measurement alone can fail.
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Síndromes de Inmunodeficiencia/diagnóstico , Mutación , Purina-Nucleósido Fosforilasa/deficiencia , Purina-Nucleósido Fosforilasa/genética , Errores Innatos del Metabolismo de la Purina-Pirimidina/diagnóstico , Adolescente , Preescolar , Reparación del ADN , Desoxiguanosina/análisis , Desoxiguanosina/metabolismo , Pruebas con Sangre Seca , Femenino , Guanosina/análisis , Guanosina/metabolismo , Humanos , Síndromes de Inmunodeficiencia/genética , Síndromes de Inmunodeficiencia/patología , Lactante , Recién Nacido , Inosina/análogos & derivados , Inosina/análisis , Inosina/metabolismo , Linfocitos/patología , Masculino , Tamizaje Neonatal , Enfermedades de Inmunodeficiencia Primaria , Errores Innatos del Metabolismo de la Purina-Pirimidina/genética , Errores Innatos del Metabolismo de la Purina-Pirimidina/patología , Espectrometría de Masas en TándemAsunto(s)
Estética Dental , Diente Impactado , Diente Canino , Encía , Humanos , Maxilar , Sonrisa , Diente Impactado/terapiaRESUMEN
BACKGROUND: Adenosine deaminase (ADA)-severe combined immunodeficiency (SCID) is caused by genetic variants that disrupt the function of ADA. In its early-onset form, it is rapidly fatal to infants. Delayed or late-onset ADA-SCID is characterized by insidious progressive immunodeficiency that leads to permanent organ damage or death. Quantification of T-cell receptor excision circles (TRECs) or tandem mass spectrometry (tandem-MS) analysis of dried blood spots (DBSs) collected at birth can identify newborns with early-onset ADA-SCID and are used in screening programs. However, it is not clear whether these analyses can identify newborns who will have delayed or late-onset ADA-SCID before symptoms appear. OBJECTIVE: We performed a retrospective study to evaluate whether tandem-MS and quantitative TREC analyses of DBSs could identify newborns who had delayed-onset ADA-SCID later in life. METHODS: We tested stored DBSs collected at birth from 3 patients with delayed-onset ADA-SCID using tandem-MS (PCT EP2010/070517) to evaluate levels of adenosine and 2'-deoxyadenosine and real-time PCR to quantify TREC levels. We also analyzed DBSs from 3 newborns with early-onset ADA-SCID and 2 healthy newborn carriers of ADA deficiency. RESULTS: The DBSs taken at birth from the 3 patients with delayed-onset ADA-SCID had adenosine levels of 10, 25, and 19 µmol/L (normal value, <1.5 µmol/L) and 2'-deoxyadenosine levels of 0.7, 2.7, and 2.4 µmol/L (normal value, <0.07 µmol/L); the mean levels of adenosine and 2'-deoxyadenosine were respectively 12.0- and 27.6-fold higher than normal values. DBSs taken at birth from all 3 patients with delayed-onset ADA deficiency had normal TREC levels, but TRECs were undetectable in blood samples taken from the same patients at the time of diagnosis. CONCLUSION: Tandem-MS but not TREC quantification identifies newborns with delayed- or late-onset ADA deficiency.
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Adenosina Desaminasa/sangre , Agammaglobulinemia/diagnóstico , Receptores de Antígenos de Linfocitos T/sangre , Inmunodeficiencia Combinada Grave/diagnóstico , Espectrometría de Masas en Tándem , Adenosina Desaminasa/deficiencia , Adenosina Desaminasa/genética , Desoxiadenosinas/metabolismo , Activación Enzimática , Eritrocitos/metabolismo , Humanos , Inmunoglobulinas/sangre , Inmunofenotipificación , Recién Nacido , Subgrupos Linfocitarios/metabolismo , Receptores de Antígenos de Linfocitos T/genética , Estudios RetrospectivosRESUMEN
In recent years, the exploration of the therapeutic potential of Salvia has gained considerable attention, leading to a growing number of scientific studies emphasizing its pharmacological properties. Despite this, therapeutic applications of Salvia remain underexploited, requiring further investigation. Iran is a major center for sage diversity in Asia, boasting 60 Salvia species, 17 of which are unique to the area. This study aimed to comprehensively explore and compare the extracts of 102 Salvia samples belonging to 20 distinct Salvia species from Iran, providing a deeper understanding of their specific polyphenol content and, consequently, their antioxidant capabilities and potential therapeutic uses. All samples were analyzed to determine the contents of total phenolics, total flavonoids, total tannin, photosynthetic pigments, and ascorbic acid, along with their antioxidant activity. These data were then combined with the forty distinct chemical fingerprints identified by ultrafast high-pressure liquid chromatography coupled with high-resolution mass spectrometry. Multivariate data analysis was employed to find correlations and differences among the huge number of data obtained and to identify Salvia species with similar phytochemical and/or antioxidant properties. The results show that each Salvia species is characterized by a distinct class of polyphenols recognized for their antidiabetic, anti-inflammatory, cardioprotective and neuroprotective properties. Overall, our findings reveal the potential of some Salvia species for targeted therapeutic applications and provide a rational basis for the development of Salvia-derived nutraceuticals, ultimately improving the prospects for the use of Salvia in medicine.
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Antioxidantes , Fitoquímicos , Extractos Vegetales , Salvia , Salvia/química , Antioxidantes/química , Antioxidantes/análisis , Antioxidantes/farmacología , Irán , Fitoquímicos/química , Fitoquímicos/análisis , Fitoquímicos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Quimiometría/métodos , Cromatografía Líquida de Alta Presión/métodos , Flavonoides/análisis , Flavonoides/química , Polifenoles/análisis , Polifenoles/químicaRESUMEN
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by bone marrow expansion and the proliferation of one or more myeloid cell lineages, predominantly driven by the expression of the constitutively active fusion product tyrosine kinase BCR:ABL1. Rarely, CML patients directly develop a blast crisis (BC), mostly of myeloid origin. CML at blast crisis with a T-cell phenotype at diagnosis, without any prior history of CML, is extremely rare. Herein, we describe one rare CML case, in a young man showing an unusual and early T-lymphoid blastic crisis at diagnosis, as the first onset of a previously unknown CML. The multidisciplinary collaboration between laboratorians and clinicians for the diagnosis and management of this atypical case was crucial in outlining both a targeted pharmacological treatment and a successful hematopoietic stem cell transplantation.
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Objectives: Coronavirus disease 2019 (COVID-19) has a wide spectrum of clinical severity. A cytokine storm is associated with COVID-19 severity. Of these, IL-6 is significantly associated with higher mortality and is also a marker for predicting disease prognosis. IL-6 may act as a target for therapeutics and, a blockade of IL-6 function by Tocilizumab has been described as a treatment of the inflammatory process COVID-19-related. This study aims to describe our experience comparing two different methods, in detail Human IL-6 Instant ELISA and the Elecsys IL-6 based on ECLIA, for the IL-6 assessment. Design and methods: IL-6 levels from serum samples of 104 COVID-19 patients, admitted to the AOU Careggi (Hospital in Florence -Italy), were assessed by using the two above-mentioned methods, and the results were analysed through Passing-Bablok regression fit and Bland-Altman plot. Results: The regression exhibited a linear relation between the methods with a regression equation (y = - 0.13 + 0.63 x; 95 % C.I. intercept = - 0.13 to 4.55; 95 % C.I. slope = 1.03 to 1.26 with R2 = 0.89, p > 0.05), showing a positive slope. The agreement of the two methods reported a bias of -25.0 pg/mL. Thus, the two methods correlate but do not agree in terms of numeric results. Conclusions: The two assays showed good comparability. However, because of the extremely wide linear range of the ECLIA, its throughput and its capacity for immune profiling, it represents an interesting emerging technology in the immunology field.
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(1) Background: Suicide is the main cause of death in Italian prisons. The largest number of inmates who killed themselves was recorded during three years of the COVID-19 pandemic. This study aimed to explore psychosocial risk factors for suicide among inmates incarcerated before and after the onset of COVID-19. (2) Methods: At prison reception, inmates underwent clinical interviews and were assessed using the Blaauw Scale and Suicide Assessment Scale. Psychological distress, measured by the Symptom Checklist-90-R, was compared between inmates admitted before and after COVID-19. Regression analyses were run to examine psychosocial vulnerabilities associated with suicidal intent in newly incarcerated individuals at risk of suicide. (3) Results: Among the 2098 newly admitted inmates (93.7% male) aged 18 to 87 years (M = 39.93; SD = 12.04), 1347 met the criteria for suicide risk, and 98 exhibited high suicidal intent. Inmates who entered prison after the onset of COVID-19 were older and had fewer social relationships. They had a higher prevalence of recidivism and substance abuse, along with elevated levels of psychological distress. An increase in perceived loss of control, anergia, obsessive-compulsive symptoms, phobic anxiety, and paranoid ideation emerged as the factors most strongly associated with high suicidal intent. (4) Conclusions: These findings support the value of psychosocial screening in promptly identifying inmates at risk of suicide, enabling the implementation of targeted, multi-professional interventions. Future research should replicate these results, with a focus on longitudinal studies that monitor the same inmates throughout their incarceration period.
RESUMEN
BACKGROUND: Since ancient times, poisoning, even serious poisoning, has been known to occur during nature walks. Intentional or unintentional ingestion of toxins of animal origin is one of the possible causes of poisoning. Bufadienolide poisoning is a critical case. This is because of its high potency and its ability to cross the blood-brain barrier. Due to the rarity of these poisonings in humans in Central Europe, their identification is often difficult. The following is a case report of a poisoning by toad eggs in an Italina child, that presented vertigo, fussiness and sleepiness. A method of toxin identification using the prince of pharmacotoxicology, liquid chromatography (LC) coupled with tandem mass spectrometry (MS/MS), and an innovative reasoning were used. This method can be applied to other poisoning cases.